We are requesting funds to purchase a PicoQuant FluoTime 200 fluorescence lifetime instrument. This instrument will augment and ultimately replace our 13 year old PTI LaserStrobe fluorescence lifetime system, which was originally purchased by the OHSU Department of Biochemistry as part of the recruitment package for Dr. Farrens. Presently, the PTI LaserStrobe is the only available system for measuring fluorescence lifetimes at OHSU and in the greater Portland area. It has proven instrumental in numerous publications and discoveries, and has served as a training opportunity for scientists and graduate students (both local and visiting) to learn about the use of fluorescence lifetimes in biological studies. However, the PTI instrument is now over 13 years old and is becoming unreliable, and maintenance is becoming difficult. Furthermore, the technology used (nitrogen-pumped dye laser with stroboscopic detection) is severely out of date, and presently does not enable precise measurements for lifetimes below ~ 500 ps, or anisotropy measurements. Thus, we need a new instrument to pursue the science being carried out by the 7 participants in this application. We considered several instruments, but ultimately we chose to go with a system from PicoQuant, as they have the longest experience in making laser-diode based fluorescence lifetime systems and their reputation for instrument stability and robustness is outstanding. The research that will be supported by this instrument includes subjects ranging from protein folding and assembly to signal transduction and metal transport, to the continued development of fluorescence methods for studying protein structure, function and dynamics. Our plan is to provide expertise, training and instrument access to scientists at OHSU and to researchers in the surrounding region. A modern state of the art fluorescence lifetime instrument is required to achieve this goal.